In order to study the function of the nonmuscle myosin II isoforms (NMII-A, II-B, and II-C), homologous recombination has been used to delete each isoform in embryonic stem cells and null mice have been generated.. Deletion of NM II-A causes lethality prior to gastrulation (E6.5) and the embryos are disorganized with defects in cell-cell adhesion and a failure to form a columnar visceral endoderm. In order to avoid the early embryonic lethality, a conditional null of NMHC II-A has been created. A neomycin-resistance cassette has been inserted into the intron prior to exon 3 and loxP sites have been inserted flanking both the neomycin cassette and the exon. Matings of these mice to mice bearing cre recombinase under the control of a cell or tissue specific promoters causes the corresponding deletion of NM II-A. Additionally, triple transgenics can be created which take advantage of the rtTA/tet operator system to confer time dependence on the deletion of a gene. This system uses ingestion of doxycycline to ultimately activate cre recombinase at a specific time. It is known that humans with MYH9 syndrome have defects in bleeding times, hearing loss, cataracts, and glomerular nephritis, Because of the severity of the kidney disorder, initial studies focus on deletion of NM II-A in kidney podocytes. Podocytes are the kidney cells which form part of the filtration barrier in the glomerulus. The NM II-A mice have been crossed to mice with cre recombinase controlled by the test operator and also mice the rtTA under control of the podocin promoter. These triple transgenics permit tissue and time dependent deletion of NM II-A in the kidney podocytes. Triple transgenics and control littermates (either without the cre recombinase, without rtTA or without the floxed NMHC II-A) are being screened by determination of glucose/creatinine ratios in urine and by kidney pathology.